SOLID TUMOR THERAPEUTICS PROGRAM (STTP): PROJECT SUMMARY The Solid Tumor Therapeutics Program (STTP) is focused on discovering somatic and germline genomic alterations that are either shared or unique across various solid tumor malignancies, and translating these discoveries into novel therapeutics that will improve the quality of life and survival for cancer patients. Two fundamental thematic areas (Genomics Technologies and Discovery, and Developmental Therapeutics [DT]) were organized to promote disease-specific studies in neuro, head and neck, thoracic, gastrointestinal, genitourinary, and gynecologic oncology. The STTP is coordinated through a leadership committee, research meetings, seminars, retreats, and other educational activities. Training for junior investigators is implemented through a mentorship plan and is supported through NCI-funded T32 (HD007499), K12 (CA167540), and Clinical and Translational Scientific Award (CTSA) educational programs. We identified areas of institutional strength and developed three research aims for the next project period. Aim 1. Develop innovative therapeutic strategies by identifying genomic, epigenomic, proteomic, and metabolomic (?omic) alterations that occur in solid tumors and by mapping their spatiotemporal evolution using preclinical models and tumor specimens. Aim 2. Determine how genomic alterations interact with immune landscapes in solid tumor malignancies; identifying these potential synergies will improve therapeutic outcomes. Aim 3. Explore the relationships among germline variants and their effects on cancer susceptibility and treatment in solid tumor malignancies, and evaluate sex-specific effects on cancer biology. These aims are designed to elucidate the effects of genetic instabilities, DNA repair defects, and specific inhibitors on solid tumor initiation, maintenance, progression, and chemoresistance. The STTP leadership facilitates and encourages collaborative interactions between disease-specific investigators and translational experts to promote translational and clinical research. These interactions are achieved through working-group meetings, focus-group meetings, seminars, and funded programs such as the NCI U54 CA224083 PDX clinical trial network and the NCI U2C CA233303 Washington University Human Tumor Atlas Research Center, which will construct detailed 4D atlases for breast cancer, glioblastoma, and pancreatic adenocarcinoma. The STTP has 47 members from 13 departments at Washington University School of Medicine. The STTP is supported by a total of $25.9 million direct costs in cancer-related funding, $5.8 million in NCI funding, and $5.8 million in other peer-reviewed funding. STTP members published 1,723 papers during 2014?2018, with 33% resulting from inter-programmatic collaborations and 24% resulting from intra-programmatic collaborations. During 2014?2018, STTP members participated in 1,511 clinical trials, 56% of which were interventional trials. These trials enrolled 32,867 patients, with 6,274 enrolled in interventional trials, 4,597 in interventional treatment trials, 1,354 in institutional interventional treatment trials, and 1,274 in early phase or first-in-human interventional treatment trials.